Lactate infusion during euglycemia but not during hypoglycemia reduces subsequent food intake

Background: Lactate can serve as an alternative substrate to glucose in cerebral energy metabolism and is assumed to protect brain functions during insulin-induced hypoglycemia. We investigated how lactate infusion modulates the effects of euglycemia and hypoglycemia on autonomic and neuroglycopenic symptoms and on subsequent food intake.

Methods: After an overnight fast of 10h, 11 healthy young men were tested according to a 2×2 design on 4 conditions, i.e. during hyperinsulinemic hypoglycemic (blood glucose at 2.8 mmol/l) and euglycemic (5.0 mmol/l) clamp experiments with concomitant lactate (2.65 mmol/kg body weight) and placebo (saline) infusions, respectively. Experiments were conducted in a double-blind manner. Subjective autonomic and neuroglycopenic symptoms were assessed by standardized questionnaires throughout the experiments. After the clamps, subjects were allowed to eat ad libitum from a standardized breakfast buffet and food intake was registered.

Results: Lactate infusion attenuated the hypoglycemia induced increase of autonomic but not of neuroglycopenic symptoms in comparison to placebo (P<0.03, P>0.73, respectively). Lactate infusion during euglycemia decreased subsequent food intake (P<0.05), whereas there was no effect of lactate on hypoglycemia induced food intake (P>0.64).

Conclusion: The decreasing influence of lactate on autonomic but not on neuroglycopenic symptoms during hypoglycemia suggests a specific effect of lactate on hypothalamic glucose sensors. Food intake was reduced by lactate after euglycemia with no differences between the other conditions. Although effects of over-fasting on food consumption in our study cannot be ruled out, this outcome suggests that lactate serves as an anorexigenic alternative energy substrate predominantly in the euglycemic range of blood glucose concentrations.